Hedyotis diffusa and Scutellaria barbata enhance the anti-ovarian cancer effect of cisplatin through network pharmacology analysis and molecular docking technology

Abstract Hedyotis diffusa Willd (HD) and Scutellaria barbata D.Don (SB) are widely used traditional Chinese herbs with detoxifying properties and anti-tumor activities. The HD-SB pairing demonstrated significant anti-tumor efficacy in cancer, however, the synergistic potential of HD-SB with cisplatin in the treatment of cancer remains poorly understood. The current work aimed to uncover the synergistic effect of HD-SB with cisplatin on ovarian cancer. In the present study, the combination of HD-SB and cisplatin exhibited a pronounced inhibitory effect on the proliferation, migration and invasion, while promoting effect on apoptosis of ovarian cancer cells. Moreover, the interaction between drug compounds and disease targets contained 277 nodes and 1395 edges, the highlighting active ingredients were quercetin, luteolin, wogonin. Among the PPI network, the top targets were TP53, STAT3, SRC, AKT1, HSP90AA1, ESR1, EGFR, TNF, PIK3R1, IL6, PIK3CA, PIK3CB. Furthermore, GO enrichemnt analysis revealed that the target intersection mainly involved in biological process, cellular component and molecular function, KEGG analysis revealed that the target intersection mainly contained the pathways in cancer, PI3K/AKT signaling pathway, proteoglycans in cancer, MAPK signaling pathway. Ultimately, the molecular docking revealed that quercetin, luteolin and wogonin exhibited significant affinity with AKT1 and PIK3CA. Mechanistically, HD-SB enhance the anti-tumor effect of cisplatin on ovarian cancer via PI3K/AKT pathway. Taken together, our study revealed that the combination of HD-SB exhibited an enhanced capacity to improve cisplatin sensitivity in ovarian cancer cells through the PI3K/AKT pathway. HD-SB in combination with cisplatin could be a potential therapeutic strategy for the treatment of ovarian cancer patients.